title: Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro.
abstract: Bone marrow mesenchymal stem cells (MSCs) transplantation has shown great promises for treating various central nervous system (CNS) diseases. However, poor viability of transplanted MSCs in injured CNS has limited the therapeutic efficiency. Oxidative stress is one of major mechanisms underlying the pathogenesis of CNS diseases and has a negative impact on the survival of transplanted MSCs. Melatonin has recently been reported to have the antioxidant and anti-apoptotic properties in serial of cells. This study was designed to investigate the protective effect and potential mechanisms of melatonin against hydrogen peroxide (H2O2)-induced apoptosis of MSCs. MSCs were pretreated with melatonin (1, 10, and 100 nM, respectively) for 30 min, followed by exposure to 400 µM H2O2 and melatonin together for 12 h. The present study reports that melatonin pretreatment significantly attenuated H2O2-induced MSC apoptosis in a dose-dependent manner. Consistently, melatonin effectively suppressed the generation of intracellular ROS, expression ratio of Bax/Bcl-2, activation of caspase-3 and expression of phospho-P38MAPK in H2O2-induced MSCs. Luzindole, a nonselective melatonin receptor antagonist, significantly counteracted melatonin's promotion effect on cell survival, indicating that melatonin exerts its protective effect on MSCs, at least in part, through the activation of melatonin receptors. The findings suggest that melatonin may be an effectively protective agent against oxidative stress-induced MSC apoptosis.
authors.affiliation: Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Shandong University School of Medicine, Jinan, PR China.
authors.forename: Fu-Wu
authors.initials: FW
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Du
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Yu-Ji
authors.initials: YJ
authors.lastname: Guo
authors.forename: Xin-Gang
authors.initials: XG
authors.lastname: Li
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects*; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008550:Melatonin / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D008550:Melatonin
keywords: APOPTOSIS; BONE MARROW MESENCHYMAL STEM CELLS; MELATONIN; OXIDATIVE STRESS